Melatonin is a methoxyindole synthesized in the retina and pineal gland. Melatonin in retina appears to play an important role in the regulation of cellular function of photoreceptors and dopamine-secreting neurons. Dopamine is involved in the regulation of melatonin biosynthesis and may also directly influence photoreceptor function. A homeostatic relationship between the melatonin and dopamine systems of retina may play a vital role in the maintenance of visual cell function. The goal of the proposed research is to characterize the melatonin system of retina and its interaction with the retinal dopamine system. To this end, the molecular and cellular mechanisms in the regulation of melatonin biosynthesis and release will be explored. Enzymes and substrates in the melatonin biosynthetic pathway will be characterized and localized, and the involvement of cyclic AMP and Ca2+ in the regulation of the system will be studied. The role of dopamine and other neurotransmitters in the regulation of the melatonin system, as well as the role of melatonin in the regulation of retinal neurotransmission, will be investigated. The interaction of melatonin and dopamine as mediators of darkness and light, respectively, will be explored with respect to the regulation of circadian rhythmicity in the retina. These studies will involve the use of cell and tissue culture, neuropharmacological, biochemical, autoradiographic, and immunocytochemical methodologies. The research is significant because it will characterize cellular and biochemical systems that may play an important role in the regulation of retinal physiology. It is anticipated that characterization of these systems will contribute to the understanding of visual cell physiology and the pathological processes that underlie photoreceptor degeneration.